期刊
NEUROCHEMISTRY INTERNATIONAL
卷 56, 期 3, 页码 394-403出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2009.11.011
关键词
Immature rats; DL-Homocysteic acid-induced seizures; Long periods of survival following the seizures; Complex I inhibition; ATP levels; 3-Nitrotyrosine; 4-Hydroxynonenal; Protein carbonyls; Free radical scavengers; (S)-3,4-DCPG; Protection
资金
- Grant Agency of the Czech Republic [309/05/2015, 309/08/0292]
- Ministry of Education, Youth and Sports of the Czech Republic [AV0Z50110509, IM6837805002]
Our previous work demonstrated the marked decrease of mitochondrial complex I activity in the cerebral cortex of immature rats during the acute phase of seizures induced by bilateral intracerebroventricular infusion Of DL-homocysteic acid (600 nmol/side) and at short time following these seizures. The present study demonstrates that the marked decrease (similar to 60%) of mitochondrial complex I activity persists during the long periods of survival, up to 5 weeks, following these seizures, i.e. periods corresponding to the development of spontaneous seizures (epileptogenesis) in this model of seizures. The decrease was selective for complex I and it was not associated with changes in the size of the assembled complex I or with changes in mitochondrial content of complex I. Inhibition of complex I was accompanied by a parallel, up to 5 weeks lasting significant increase (15-30%) of three independent mitochondrial markers of oxidative damage, 3-nitrotyrosine, 4-hydroxynonenal and protein carbonyls. This suggests that oxidative modification may be most likely responsible for the sustained deficiency of complex I activity although potential role of other factors cannot be excluded. Pronounced inhibition of complex I was not accompanied by impaired ATP production, apparently due to excess capacity of complex I documented by energy thresholds. The decrease of complex I activity was substantially reduced by treatment with selected free radical scavengers. It could also be attenuated by pretreatment with (S)-3,4-DCPG (an agonist for subtype 8 of group III metabotropic glutamate receptors) which had also a partial antiepileptogenic effect. It can be assumed that the persisting inhibition of complex I may lead to the enhanced production of reactive oxygen and/or nitrogen species, contributing not only to neuronal injury demonstrated in this model of seizures but also to epileptogenesis. (C) 2009 Elsevier Ltd. All rights reserved.
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